|In addition to the traditional inheritance patterns, several other mechanisms have been described. They involve genetically determined structures and can produce various disorders.
|Mosaicism: Mosaicism is the presence of >= 2 cell lines differing in genotype or karyotype but derived from one zygote. Mutations are likely to occur during the cell divisions of any large multicellular organism even though the genetic apparatus of cell division is usually accurate and many mechanisms exist to repair mistakes made during replication. It is estimated that each time a cell divides, four or five changes occur in the genome. Thus, any large multicellular organism will have subclones of cells having a slightly different genetic makeup. These somatic mutations （ie, mutations during mitotic cell division） may not lead to disease but to disorders in which patchy changes occur. Molecular genetic techniques have shown mutations in the abnormal cells involved in a patch compared with the normal surrounding supporting tissues. For example, in McCune-Albright syndrome, there are patchy dysplastic changes in the bone, abnormalities of endocrine glands, patchy pigmentary changes, and occasionally abnormalities in the heart or liver. Persons with these abnormalities in all cells would die, so the condition would not be passed on to the next generation, but they survive because normal tissue supports the abnormal tissue. Occasionally, in a single-gene disorder, a parent seems to have a milder form but is actually a mosaic; their more severely affected child would have received a germ cell with the mutant allele and thus would have the abnormality present in every cell. Chromosomal mosaicism occurs in some embryos and can be demonstrated in the placenta on chorionic villus sampling. Most chromosomally abnormal embryos and fetuses abort spontaneously. However, the development of normal cells may support certain chromosomal abnormalities, allowing offspring to be born alive.
|Genomic imprinting: Genomic imprinting is the differential expression of genetic material depending on whether it has been inherited from the father or mother. Genomic imprinting is tissue-specific and time-in-development-specific. Bi-allelic or biparental expression of alleles may be present in some tissues and uniparental expression in other tissues. Angelman syndrome and Prader-Willi syndrome can both be produced by deletions of chromosome 15. Groups of specific genes exist in close proximity on chromosome 15 with only paternal or maternal expression. Depending on whether the deleted chromosome is paternally or maternally inherited, a different syndrome will be produced.
|Many areas on several chromosomes have this type of parent-of-origin effect. The involved genes seem to be related to growth and behavior in early development. Some of these genes are also involved in tumors and cancers. Genomic imprinting must be considered in disorders that appear to have skipped a generation.
|Uniparental disomy: Uniparental disomy occurs when two chromosomes of a pair are inherited from only one parent. This is very rare and is thought to involve trisomy rescue; ie, the zygote started off as a trisomy and one of the three chromosomes was lost, leading to uniparental disomy in 1/3 of cases. Imprinting effects may be seen because genetic information from the other parent is absent. In addition, if the same chromosome is in duplicate （isodisomy） and that chromosome carries an abnormal allele for an autosomal recessive disorder, a person with uniparental disomy can have an autosomal recessive disorder although only one parent is a carrier. Vestigial chromosomal abnormalities in some tissues must be considered in the presence of uniparental disomy.
|Triplet repeat, unstable mutations: A triplet repeat is an unusual type of mutation in which a triplet of nucleotides increases in number within a gene （a normal gene has relatively few tandem triplet repeats）. This type of mutation has been recognized to occur in several disorders, particularly those involving the CNS. When the gene is transmitted from one generation to the next, or sometimes within the body as cells divide, the triplet repeat can expand and enlarge to a point at which the gene stops functioning normally. Examples include myotonic dystrophy, Huntington's disease, fragile X mental retardation, and several other neurologic disorders. The number of repeats may increase dramatically in the formation of germ cells or in certain tissues as the embryo and fetus develop. Expansion may be greater when transmitted from one parent （eg, the mother in myotonic dystrophy, the father in Huntington's disease）; thus, a parent-of-origin effect and anticipation can be observed. This type of mutation is detected by molecular studies.
|Anticipation: Anticipation occurs when a disorder has an earlier age of onset and severity of expression in each successive generation. It may occur because a parent is a mosaic, and the child has the full mutation in all cells. Triplet repeat expansion may demonstrate anticipation when the number of repeats increases with each generation.